This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Bosch lab is interested in malarial proteins involved in invasion and egress of the parasite into or from various cell types in the human liver, red blood cells as well as in the Mosquito vector. We aim at impairing the parasite's proliferation through small molecule inhibitors for key proteins through structure based drug design in conjunction with x-ray crystallography. The Prigge lab is interested in the structural biology of key proteins from malaria and tuberculosis. Current protein crystals include proteins involved in pathogen persistence in tuberculosis and sexual differentiation in malaria. The Bailey lab performs structure function studies of a newly characterized acquired immune system in prokaryotes, which shares some of the basic principles of eukaryotic RNAi. Through the analysis of crystal structures and functional data we hope to discern the molecular mechanisms underpinning this immunity. To this end we have obtained crystals of several of the proteins involved.